Characterizing the conductance underlying depolarization-induced slow current in cerebellar Purkinje cells

Yu Shin Kim, Eunchai Kang, Yuichi Makino, Sungjin Park, Jung Hoon Shin, Hongjun Song, Pierre Launay, David J. Linden

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Brief strong depolarization of cerebellar Purkinje cells produces a slow inward cation current [depolarization- induced slow current (DISC)]. Previous work has shown that DISC is triggered by voltage-sensitive Ca influx in the Purkinje cell and is attenuated by blockers of vesicular loading and fusion. Here, we have sought to characterize the ion channel(s) underlying the DISC conductance. While the brief depolarizing steps that triggered DISC were associated with a large Ca transient, the onset of DISC current corresponded only with the Ca transient decay phase. Furthermore, substitution of external Na with the impermeant cation N-methyl- D-glucamine produced a complete and reversible block of DISC, suggesting that the DISC conductance was not Ca permeant. Transient receptor potential cation channel, subfamily M, members 4 (TRPM4) and 5 (TRPM5) are nonselective cation channels that are opened by Ca transients but do not flux Ca. They are expressed in Purkinje cells of the posterior cerebellum, where DISC is large, and, in these cells, DISC is strongly attenuated by nonselective blockers of TRPM4/5. However, measurement of DISC currents in Purkinje cells derived from TRPM4 null, TRPM5 null, and double null mice as well as wild-type mice with TRPM4 short hairpin RNA knockdown showed a partial attenuation with 35-46% of current remaining. Thus, while the DISC conductance is Ca triggered, Na permeant, and Ca impermeant, suggesting a role for TRPM4 and TRPM5, these ion channels are not absolutely required for DISC.

Original languageEnglish (US)
Pages (from-to)1174-1181
Number of pages8
JournalJournal of Neurophysiology
Volume109
Issue number4
DOIs
StatePublished - Feb 15 2013
Externally publishedYes

Fingerprint

Purkinje Cells
Cations
Ion Channels
Transient Receptor Potential Channels
Cerebellum
Small Interfering RNA

Keywords

  • Calcium
  • Cation current
  • TRPM4
  • TRPM5

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Kim, Y. S., Kang, E., Makino, Y., Park, S., Shin, J. H., Song, H., ... Linden, D. J. (2013). Characterizing the conductance underlying depolarization-induced slow current in cerebellar Purkinje cells. Journal of Neurophysiology, 109(4), 1174-1181. https://doi.org/10.1152/jn.01168.2011

Characterizing the conductance underlying depolarization-induced slow current in cerebellar Purkinje cells. / Kim, Yu Shin; Kang, Eunchai; Makino, Yuichi; Park, Sungjin; Shin, Jung Hoon; Song, Hongjun; Launay, Pierre; Linden, David J.

In: Journal of Neurophysiology, Vol. 109, No. 4, 15.02.2013, p. 1174-1181.

Research output: Contribution to journalArticle

Kim, YS, Kang, E, Makino, Y, Park, S, Shin, JH, Song, H, Launay, P & Linden, DJ 2013, 'Characterizing the conductance underlying depolarization-induced slow current in cerebellar Purkinje cells', Journal of Neurophysiology, vol. 109, no. 4, pp. 1174-1181. https://doi.org/10.1152/jn.01168.2011
Kim, Yu Shin ; Kang, Eunchai ; Makino, Yuichi ; Park, Sungjin ; Shin, Jung Hoon ; Song, Hongjun ; Launay, Pierre ; Linden, David J. / Characterizing the conductance underlying depolarization-induced slow current in cerebellar Purkinje cells. In: Journal of Neurophysiology. 2013 ; Vol. 109, No. 4. pp. 1174-1181.
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